Manufacturing of PAV-ONE, a Permeator against Vacuum Mock-Up with Niobium Membrane

The Permeator Against Vacuum (PAV) is one of the proposed technologies for the Tritium Extraction System of the WCLL BB (Water-Cooled Lithium-Lead Breeding Blanket) of the EU DEMO reactor. In this paper, the manufacturing of the first PAV mock-up with a niobium membrane with a cylindrical configuration is presented. This work aimed to demonstrate the possibility of manufacturing a relevant-size PAV to be later tested in the TRIEX-II facility. The adopted prototypical solutions are described in detail, starting with the methodology developed to join the Nb tubes with a 10CrMo9-10 (A182 F22) plate. Dedicated manufacturing and welding procedures, based on vacuum brazing with a nickel-based brazing alloy, were developed to solve the problem. This new kind of brazing was first analyzed to check the morphology of the joint and then tested to check its capability to withstand the TRIEX-II operative conditions. In parallel, the compatibility with a lithium-lead environment was analyzed by exposing samples of niobium and 10CrMo9-10 (A335 P22) to a flow of the eutectic alloy at 500 °C up to 4000 h. Finally, the PAV mock-up was installed in the TRIEX-II facility

Antigen Retrieval and Its Effect on the MALDI-MSI of Lipids in Formalin-Fixed Paraffin-Embedded Tissue

Formalin-fixed paraffin-embedded (FFPE) tissue represents the primary source of clinical tissue and is routinely used in MALDI-MSI studies. However, it is not particularly suitable for lipidomics imaging given that many species are depleted during tissue processing. Irrespective, a number of solvent-resistant lipids remain, but their extraction may be hindered by the cross-link between proteins. Therefore, an antigen retrieval step could enable the extraction of a greater number of lipids and may provide information that is complementary to that which can be obtained from other biomolecules, such as proteins. In this short communication, we aim to address the effect of performing antigen retrieval prior to MALDI-MSI of lipids in FFPE tissue. As a result, an increased number of lipid signals could be detected and may have derived from lipid species that are known to be implicated in the lipid-protein cross-linking that is formed as a result of formalin fixation. Human renal cancer tissue was used as a proof of concept to determine whether using these detected lipid signals were also able to highlight the histopathological regions that were present. These preliminary findings may highlight the potential to enhance the clinical relevance of the lipidomic information obtained from FFPE tissue

In-Depth Mapping of the Urinary N-Glycoproteome: Distinct Signatures of ccRCC-related Progression

Protein N-glycosylation is one of the most important post-translational modifications and is involved in many biological processes, with aberrant changes in protein N-glycosylation patterns being closely associated with several diseases, including the progression and spreading of tumours. In light of this, identifying these aberrant protein glycoforms in tumours could be useful for understanding the molecular mechanism of this multifactorial disease, developing specific biomarkers and finding novel therapeutic targets. We investigated the urinary N-glycoproteome of clear cell renal cell carcinoma (ccRCC) patients at different stages (n = 15 at pT1 and n = 15 at pT3), and of non-ccRCC subjects (n = 15), using an N-glyco-FASP-based method. Using label-free nLC-ESI MS/MS, we identified and quantified several N-glycoproteins with altered expression and abnormal changes affecting the occupancy of the glycosylation site in the urine of RCC patients compared to control. In particular, nine of them had a specific trend that was directly related to the stage progression: CD97, COCH and P3IP1 were up-expressed whilst APOB, FINC, CERU, CFAH, HPT and PLTP were down-expressed in ccRCC patients. Overall, these results expand our knowledge related to the role of this post-translational modification in ccRCC and translation of this information into pre-clinical studies could have a significant impact on the discovery of novel biomarkers and therapeutic target in kidney cancer

Detecting Proteomic Indicators to Distinguish Diabetic Nephropathy from Hypertensive Nephrosclerosis by Integrating Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging with High-Mass Accuracy Mass Spectrometry

Introduction: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to -end-stage renal disease. Patients are treated primarily through the management of cardiovas-cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth-ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion-ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). Results: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. Discussion/conclusion: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians

Il controllo del sanguinamento nella protesi totale di ginocchio

Total knee arthroplasty is associated with high blood loss and high incidence of blood transfusion. In order to reduce the bleeding after total knee replacement, several strategies have been used simultaneously, including surgical and medical techniques, technological devices and drugs. The synergistic use of the available methods may be a good solution for reducing blood loss and requests for autologous blood transfusion

Brownian motion of graphene.

Brownian motion is a manifestation of the fluctuation-dissipation theorem of statistical mechanics. It regulates systems in physics, biology, chemistry, and finance. We use graphene as prototype material to unravel the consequences of the fluctuation-dissipation theorem in two dimensions, by studying the Brownian motion of optically trapped graphene flakes. These orient orthogonal to the light polarization, due to the optical constants anisotropy. We explain the flake dynamics in the optical trap and measure force and torque constants from the correlation functions of the tracking signals, as well as comparing experiments with a full electromagnetic theory of optical trapping. The understanding of optical trapping of two-dimensional nanostructures gained through our Brownian motion analysis paves the way to light-controlled manipulation and all-optical sorting of biological membranes and anisotropic macromolecules

The miR-15/107 Family of microRNA Genes Regulates CDK5R1/p35 with Implications for Alzheimer’s Disease Pathogenesis

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) encodes p35, the main activatory subunit of cyclin-dependent kinase 5 (CDK5). The p35/CDK5 active complex plays a fundamental role in brain development and functioning, but its deregulated activity has also been implicated in various neurodegenerative disorders, including Alzheimer\u2019s disease (AD). CDK5R1 displays a large and highly evolutionarily conserved 3\u2032-untranslated region (3\u2032-UTR), a fact that has suggested a role for this region in the post-transcriptional control of CDK5R1 expression. Our group has recently demonstrated that two miRNAs, miR-103 and miR-107, regulate CDK5R1 expression and affect the levels of p35. MiR-103 and miR-107 belong to the miR-15/107 family, a group of evolutionarily conserved miRNAs highly expressed in human cerebral cortex. In this work, we tested the hypothesis that other members of this group of miRNAs, in addition to miR-103 and miR-107, were able to modulate CDK5R1 expression. We provide evidence that several miRNAs belonging to the miR-15/107 family regulate p35 levels. BACE1 expression levels were also found to be modulated by different members of this family. Furthermore, overexpression of these miRNAs led to reduced APP phosphorylation levels at the CDK5-specific Thr668 residue. We also show that miR-15/107 miRNAs display reduced expression levels in hippocampus and temporal cortex, but not in cerebellum, of AD brains. Moreover, increased CDK5R1 mRNA levels were observed in AD hippocampus tissues. Our results suggest that the downregulation of the miR-15/107 family might have a role in the pathogenesis of AD by increasing the levels of CDK5R1/p35 and consequently enhancing CDK5 activity

Detecting proteomic indicators to distinguish diabetic nephropathy from hypertensive nephrosclerosis by integrating matrix-assisted laser desorption/ionization mass spectrometry imaging with high-mass accuracy mass spectrometry

Introduction: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to -end-stage renal disease. Patients are treated primarily through the management of cardiovas-cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth-ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion-ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). Results: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. Discussion/Conclusion: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.Proteomic

Advances in infrastructures and tools for multiagent systems

In the last few years, information system technologies have focused on solving challenges in order to develop distributed applications. Distributed systems can be viewed as collections of service-provider and ser vice-consumer components interlinked by dynamically defined workflows (Luck and McBurney 2008).Alberola Oltra, JM.; Botti Navarro, VJ.; Such Aparicio, JM. (2014). Advances in infrastructures and tools for multiagent systems. Information Systems Frontiers. 16:163-167. doi:10.1007/s10796-014-9493-6S16316716Alberola, J. M., Búrdalo, L., Julián, V., Terrasa, A., & García-Fornes, A. (2014). An adaptive framework for monitoring agent organizations. Information Systems Frontiers, 16(2). doi: 10.1007/s10796-013-9478-x .Alfonso, B., Botti, V., Garrido, A., & Giret, A. (2014). A MAS-based infrastructure for negotiation and its application to a water-right market. Information Systems Frontiers, 16(2). doi: 10.1007/s10796-013-9443-8 .Andrighetto, G., Castelfranchi, C., Mayor, E., McBreen, J., López-Sánchez, M., & Parsons, S. (2013). (Social) norm dynamics. In G. Andrighetto, G. Governatori, P. Noriega, & L. W. van der Torre (Eds.), Normative multi-agent systems (pp. 135–170). Dagstuhl: Schloss Dagstuhl--Leibniz-Zentrum fuer Informatik.Baarslag, T., Fujita, K., Gerding, E. H., Hindriks, K., Ito, T., Jennings, N. R., et al. (2013). Evaluating practical negotiating agents: results and analysis of the 2011 international competition. Artificial Intelligence, 198, 73–103.Boissier, O., Bordini, R. H., Hübner, J. F., Ricci, A., & Santi, A. (2013). Multi-agent oriented programming with JaCaMo. Science of Computer Programming, 78(6), 747–761.Campos, J., Esteva, M., López-Sánchez, M., Morales, J., & Salamó, M. (2011). Organisational adaptation of multi-agent systems in a peer-to-peer scenario. Computing, 91(2), 169–215.Carrera, A., Iglesias, C. A., & Garijo, M. (2014). Beast methodology: an agile testing methodology for multi-agent systems based on behaviour driven development. Information Systems Frontiers, 16(2). doi: 10.1007/s10796-013-9438-5 .Criado, N., Such, J. M., & Botti, V. (2014). Norm reasoning services. Information Systems Frontiers, 16(2). doi: 10.1007/s10796-013-9444-7 .Del Val, E., Rebollo, M., & Botti, V. (2014). Enhancing decentralized service discovery in open service-oriented multi-agent systems. Journal of Autonomous Agents and Multi-Agent Systems, 28(1), 1–30.Denti, E., Omicini, A., & Ricci, A. (2002). Coordination tools for MAS development and deployment. Applied Artificial Intelligence, 16(9–10), 721–752.Dignum, V., & Dignum, F. (2012). A logic of agent organizations. Logic Journal of IGPL, 20(1), 283–316.Ferber, J., & Gutknecht, O. (1998). A meta-model for the analysis and design of organizations in multi-agent systems. In Multi agent systems. Proceedings. International Conference on (pp. 128–135). IEEE.Fogués, R. L., Such, J. M., Espinosa, A., & Garcia-Fornes, A. (2014). BFF: a tool for eliciting tie strength and user communities in social networking services. Information Systems Frontiers, 16(2). doi: 10.1007/s10796-013-9453-6 .Garcia, E., Giret, A., & Botti, V. (2011). Evaluating software engineering techniques for developing complex systems with multiagent approaches. Information and Software Technology, 53(5), 494–506.Garcia-Fornes, A., Hübner, J., Omicini, A., Rodriguez-Aguilar, J., & Botti, V. (2011). Infrastructures and tools for multiagent systems for the new generation of distributed systems. Engineering Applications of Articial Intelligence, 24(7), 1095–1097.Jennings, N., Faratin, P., Lomuscio, A., Parsons, S., Sierra, C., & Wooldridge, M. (2001). Automated negotiation: prospects, methods and challenges. International Journal of Group Decision and Negotiation, 10(2), 199–215.Jung, Y., Kim, M., Masoumzadeh, A., & Joshi, J. B. (2012). A survey of security issue in multi-agent systems. Artificial Intelligence Review, 37(3), 239–260.Kota, R., Gibbins, N., & Jennings, N. R. (2012). Decentralized approaches for self-adaptation in agent organizations. ACM Transactions on Autonomous and Adaptive Systems (TAAS), 7(1), 1.Kraus, S. (1997). Negotiation and cooperation in multi-agent environments. Artificial Intelligence, 94(1), 79–97.Lin, Y. I., Chou, Y. W., Shiau, J. Y., & Chu, C. H. (2013). Multi-agent negotiation based on price schedules algorithm for distributed collaborative design. Journal of Intelligent Manufacturing, 24(3), 545–557.Luck, M., & McBurney, P. (2008). Computing as interaction: agent and agreement technologies.Luck, M., McBurney, P., Shehory, O., & Willmott, S. (2005). Agent technology: Computing as interaction (A roadmap for agent based computing). AgentLink.Ossowski, S., & Menezes, R. (2006). On coordination and its significance to distributed and multiagent systems. Concurrency and Computation: Practice and Experience, 18(4), 359–370.Ossowski, S., Sierra, C., & Botti. (2013). Agreement technologies: A computing perspective. In Agreement Technologies (pp. 3–16). Springer Netherlands.Pinyol, I., & Sabater-Mir, J. (2013). Computational trust and reputation models for open multi-agent systems: a review. Artificial Intelligence Review, 40(1), 1–25.Ricci, A., Piunti, M., & Viroli, M. (2011). Environment programming in multi-agent systems: an artifact-based perspective. Autonomous Agents and Multi-Agent Systems, 23(2), 158–192.Sierra, C., & Debenham, J. (2006). Trust and honour in information-based agency. In Proceedings of the 5th international conference on autonomous agents and multi agent systems, (p. 1225–1232). New York: ACM.Sierra, C., Botti, V., & Ossowski, S. (2011). Agreement computing. KI-Knstliche Intelligenz, 25(1), 57–61.Vasconcelos, W., García-Camino, A., Gaertner, D., Rodríguez-Aguilar, J. A., & Noriega, P. (2012). Distributed norm management for multi-agent systems. Expert Systems with Applications, 39(5), 5990–5999.Wooldridge, M. (2002). An introduction to multiagent systems. New York: Wiley.Wooldridge, M., & Jennings, N. R. (1995). Intelligent agents: theory and practice. Knowledge Engineering Review, 10(2), 115–152